Copy number variants in neurexin genes: phenotypes and mechanisms.
Journal
Current opinion in genetics & development
ISSN: 1879-0380
Titre abrégé: Curr Opin Genet Dev
Pays: England
ID NLM: 9111375
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
12
10
2020
revised:
17
02
2021
accepted:
23
02
2021
pubmed:
24
3
2021
medline:
30
12
2021
entrez:
23
3
2021
Statut:
ppublish
Résumé
Neurexins are central to trans-synaptic cell adhesion and signaling during synapse specification and maintenance. The past two decades of human genetics research have identified structural variations in the neurexin gene family, in particular NRXN1 copy number variants (CNVs), implicated in multiple neuropsychiatric and developmental disorders. The heterogeneity and reduced penetrance of NRXN1 deletions, in addition to the pleiotropic, circuit-specific functions of NRXN1, present substantial obstacles to understanding how compromised NRXN1 function predisposes individuals to neuropsychiatric disorders. Here, we provide an updated review of NRXN1 genetics in disease, followed by recently published work using both human induced pluripotent stem cell (iPSC) derived systems and animal models to understand the mechanisms of disease pathophysiology. Finally, we suggest our outlook on how the field should progress to improve our understanding of neurexin mediated disease pathogenesis. We believe that understanding how structural genetic variants in NRXN1 contribute to disease pathophysiology requires parallel approaches in iPSC and mouse model systems, each leveraging their unique strengths - analysis of genetic interactions and background effects in iPSCs and neural circuit and behavioral analysis in mice.
Identifiants
pubmed: 33756113
pii: S0959-437X(21)00031-9
doi: 10.1016/j.gde.2021.02.010
pmc: PMC8491281
mid: NIHMS1685804
pii:
doi:
Substances chimiques
Calcium-Binding Proteins
0
NRXN1 protein, human
0
Neural Cell Adhesion Molecules
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
64-70Subventions
Organisme : NIMH NIH HHS
ID : R00 MH099243
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH115030
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH122519
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
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